C-reactive protein modulates myeloid derived suppressor cell function and signaling.

Abstract

Abstract Recently, we provided evidence that C-reactive protein (CRP) plays a causal role in acute kidney injury (AKI) i.e., human CRP exacerbates AKI in CRP transgenic mice (CRPtg) and AKI severity is lessened in CRP knockout mice. The CRP effect in CRPtg was associated with significantly increased renal infiltration by myeloid derived suppressor cells (MDSC). Subsequently, we showed that the AKI exacerbating influence of CRP in CRPtg could be blocked by depletion of MDSCs. In the present work we sought to define the impact of CRP on MDSC ontogeny and function. Using wild type mouse bone marrow (BM) we derived MDSCs and established that CRP enhances their ability to suppress CD3ɛ/CD28-stimulated T cell proliferation in vitro. By flow cytometry we verified that mouse BM-MDSCs express variable amounts of three CRP receptors: LOX-1, FcγRI, and FcγRIIB. Expression of the latter on BM-MDSCs was upregulated upon CRP exposure, as demonstrated by flow cytometry. Furthermore, preliminary data obtained from studies using BM-MDSCs derived from FcγRIIB deficient mice suggest that FcγRIIB participates in CRP-mediated signaling. In their sum, these data suggest that CRP-mediated augmentation of MDSC suppressive function is FcγRIIB-dependent. Ongoing work seeks to define the consequences of CRP-mediated modulation of MDSC functions in vivo and to explore whether FcγRIIB and other CRP receptors are involved.